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Thromb Haemost 2011; 106(04): 609-616
DOI: 10.1160/TH11-03-0204
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Binding characteristics of thrombin-activatable fibrinolysis inhibitor to streptococcal surface collagen-like proteins A and B

Mercedes Valls Serón
1   Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
3   Clinical Chemistry and Haematology, University Medical Center, Utrecht University, Utrecht, the Netherlands
,
Tom Plug
1   Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
,
J. Arnoud Marquart
1   Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
,
Pauline F. Marx
1   Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
,
Heiko Herwald
2   Department of Clinical Sciences, Section for Clinical and Experimental Infection Medicine, Lund University
,
Philip G. de Groot
3   Clinical Chemistry and Haematology, University Medical Center, Utrecht University, Utrecht, the Netherlands
,
Joost C. M. Meijers
1   Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
› Author Affiliations Financial support: This work was supported by the Netherlands Organization for Scientific Research (grant number ZonMW 91207002, to J. C. M. Meijers and P. G. de Groot).
Further Information

Publication History

Received: 29 March 2011

Accepted after major revision: 22 June 2011

Publication Date:
29 November 2017 (online)

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Summary

Streptococcus pyogenes is the causative agent in a wide range of diseases in humans. Thrombin-activatable fibrinolysis inhibitor (TAFI) binds to collagen-like proteins SclA and SclB at the surface of S. pyogenes. Activation of TAFI at this surface redirects inflammation from a transient to chronic state by modulation of the kallikrein/kinin system. We investigated TAFI binding characteristics to SclA/SclB. Thirty-four overlapping TAFI peptides of ∼20 amino acids were generated. Two of these peptides (P18: residues G205-S221, and P19: R214-D232) specifically bound to SclA/SclB with high affinity, and competed in a dose-dependent manner with TAFI binding to SclA/SclB. In another series of experiments, the binding properties of activated TAFI (TAFIa) to SclA/SclB were studied with a quadruple TAFI mutant (TAFI-IIYQ) that after activation is a 70-fold more stable enzyme than wild-type TAFIa. TAFI and TAFI-IIYQ bound to the bacterial proteins with similar affinities. The rate of dissociation was different between the proenzyme (both TAFI and TAFI-IIYQ) and the stable enzyme TAFIa-IIYQ. TAFIa-IIYQ bound to SclA/ SclB, but dissociated faster than TAFI-IIYQ. In conclusion, the bacterial proteins SclA and SclB bind to a TAFI fragment encompassing residues G205-D232. Binding of TAFI to the bacteria may allow activation of TAFI, whereafter the enzyme easily dissociates.

Keywords

TAFI - collagen-like proteins - protein binding - Streptococcus pyogenes
 

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